Among the various routes of drug administration, an oral route remains the preferred route for the administration of therapeutic agents due to low cost, ease of administration and high level of patient compliance. However, hepatic first pass metabolism and drug degradation within a gastrointestinal (GI) tract significantly prohibits an oral administration of certain classes of drugs. Consequently, other absorptive mucosae are being considered as potential sites for drug administration including the mucosal linings of the nasal, rectal, vaginal, ocular, and oral cavity. These transmucosal routes of drug delivery offer distinct advantages over a peroral administration for systemic drug delivery, such as possible bypass of the first pass effect and avoidance of pre-systemic elimination within the GI tract.
However, drug delivery through an oral cavity is considered to be a promising alternative, due to its unique physiological features and high patient compliance. Various dosage forms like solutions, lozenges, pastilles, chewing gums, sprays, patches, films, hydrogels, hollow fibres and microspheres are available for drug delivery through the oral cavity.
The majority of the commercially available formulations for drug delivery through the oral cavity are solid dosage forms such as lozenges and pastilles.
Lozenges and pastilles are solid preparations that are intended to dissolve or disintegrate slowly in the mouth. They contain one or more medicaments usually in a flavored and sweetened base. These are most often used for localized effects in the mouth but can also be used for systemic effect if the drug is well absorbed through the buccal lining. The drugs which can be successfully delivered to the site of its action through this route include analgesics, anesthetics, antiseptics, antimicrobials, antitussives, anti-nausants, antacids and decongestants.
However, high sugar content is a major drawback associated with lozenges and pastilles prepared by conventional methods. Further, lozenges get break down into pieces followed by accidental swallowing which in turn results in excessive transfer of active ingredient in GI tract. Furthermore, it is not comfortable for a patient to keep a hard product like lozenges in the buccal cavity for a prolonged period.
Curcumin is diarylheptanoid and principal curcuminoid of the popular Indian spice turmeric (Curcuma longa). The other two curcuminoids are desmethoxycurcumin and bis-desmethoxycurcumin. The curcuminoids are natural phenols that are responsible for the yellow color of turmeric. Curcumin is insoluble in water and is impermeable through the cell membrane. Traditionally, curcumin is commonly utilized in many therapeutic remedies, either alone or in conjunction with other natural substances. Accumulated evidence indicates that curcumin is associated with a great variety of pharmacological activities, such as anti-inflammatory, and antioxidant activities.
Curcumin acts by way of modulating multiple molecular targets, cell signaling proteins, cell cycle proteins, cytokines and chemokines, enzymes, receptors and cell surface adhesion molecules. It is known that the potential health benefits of curcumin are limited by its poor solubility, low absorption from the gut, rapid metabolism and rapid systemic elimination.
The major portion of ingested curcumin is excreted through the feces un-metabolized whereas the small portion which is absorbed is extensively converted to its water-soluble metabolites, glucuronides and sulfates. Microbial metabolism of curcumin yields dihydrocurcumin, and tetrahydrocurcumin through NADPH dependent reduction. Curcumin and its reduced metabolites are conjugated with monoglucuronide via beta-glucuronidase, a monosulfate via sulfatase enzymes and a mixed sulfate/glucuronide, resulting in curcumin-glucuronoside, dihydocurcumin glucuronoside, tetrahydrocurcumin glucuronoside or corresponding monosulfate and mixed sulfate/glucuronoside. Different formulations have been tried in recent past to improve the absorption of curcumin including nanocrystals, emulsions, liposomes, self-assemblies and nanogels.
Curcumin is suggested as a potent anti-microbial agent however, inadequate emphasis has been given on the development of a dosage form, containing curcumin as an active ingredient having anti-inflammatory activity. Further, available oral dosage forms containing curcumin do not produce desired local and/or systemic action.
Accordingly, it is desirable to provide a palatable, clinically efficacious, well-tolerable and long-acting soft pastille containing curcumin as an active ingredient.